Cdc37 has distinct roles in protein kinase quality control that protect nascent chains from degradation and promote posttranslational maturation

Cdc37 is a molecular chaperone that functions with Hsp90 to promote protein kinase folding. Analysis of 65 Saccharomyces cerevisiae protein kinases (∼50% of the kinome) in a cdc37 mutant strain showed that 51 had decreased abundance compared with levels in the wild-type strain. Several lipid kinases also accumulated in reduced amounts in the cdc37 mutant strain. Results from our pulse-labeling studies showed that Cdc37 protects nascent kinase chains from rapid degradation shortly after synthesis. This degradation phenotype was suppressed when cdc37 mutant cells were grown at reduced temperatures, although this did not lead to a full restoration of kinase activity. We propose that Cdc37 functions at distinct steps in kinase biogenesis that involves protecting nascent chains from rapid degradation followed by its folding function in association with Hsp90. Our studies demonstrate that Cdc37 has a general role in kinome biogenesis

ACR Appropriateness Criteria® Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer

Patients with locally advanced invasive breast cancers are often treated with neoadjuvant chemotherapy prior to definitive surgical intervention. The primary aims of this approach are to: 1) reduce tumor burden thereby permitting breast conservation rather than mastectomy; 2) promptly treat possible metastatic disease, whether or not it is detectable on preoperative staging; and 3) potentially tailor future chemotherapeutic decisions by monitoring in-vivo tumor response. Accurate radiological assessment permits optimal management and planning in this population. However, assessment of tumor size and response to treatment can vary depending on the modality used, the measurement technique (such as single longest diameter, 3-D measurements, or calculated tumor volume), and varied response of different tumor subtypes to neoadjuvant chemotherapy (such as concentric shrinkage or tumor fragmentation). As discussed in further detail, digital mammography, digital breast tomosynthesis, US and MRI represent the key modalities with potential to help guide patient management. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment

ACR Appropriateness Criteria

© 2018 American College of Radiology Breast pain is a common complaint. However, in the absence any accompanying suspicious clinical finding (eg, lump or nipple discharge), the association with malignancy is very low (0%-3.0%). When malignancy-related, breast pain tends to be focal (less than one quadrant) and persistent. Pain that is clinically insignificant (nonfocal [greater than one quadrant], diffuse, or cyclical) requires no imaging beyond what is recommended for screening. In cases of pain that is clinically significant (focal and noncyclical), imaging with mammography, digital breast tomosynthesis (DBT), and ultrasound are appropriate, depending on the patient\u27s age. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment

ACR Appropriateness Criteria \u3csup\u3e®\u3c/sup\u3e Breast Pain

© 2018 American College of Radiology Breast pain is a common complaint. However, in the absence any accompanying suspicious clinical finding (eg, lump or nipple discharge), the association with malignancy is very low (0%-3.0%). When malignancy-related, breast pain tends to be focal (less than one quadrant) and persistent. Pain that is clinically insignificant (nonfocal [greater than one quadrant], diffuse, or cyclical) requires no imaging beyond what is recommended for screening. In cases of pain that is clinically significant (focal and noncyclical), imaging with mammography, digital breast tomosynthesis (DBT), and ultrasound are appropriate, depending on the patient\u27s age. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment

ACR Appropriateness Criteria ® Breast Cancer Screening

Breast cancer screening recommendations are based on risk factors. For average-risk women, screening mammography and/or digital breast tomosynthesis is recommended beginning at age 40. Ultrasound (US) may be useful as an adjunct to mammography for incremental cancer detection in women with dense breasts, but the balance between increased cancer detection and the increased risk of a false-positive examination should be considered in the decision. For intermediate-risk women, US or MRI may be indicated as an adjunct to mammography depending upon specific risk factors. For women at high risk due to prior mantle radiation between the ages of 10 to 30, mammography is recommended starting 8 years after radiation therapy but not before age 25. For women with a genetic predisposition, annual screening mammography is recommended beginning 10 years earlier than the affected relative at the time of diagnosis but not before age 30. Annual screening MRI is recommended in high-risk women as an adjunct to mammography. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment

ACR Appropriateness Criteria ® Evaluation of Nipple Discharge

Appropriate imaging evaluation of nipple discharge depends the nature of the discharge. Imaging is not indicated for women with physiologic nipple discharge. For evaluation of pathologic nipple discharge, multiple breast imaging modalities are rated for evidence-based appropriateness under various scenarios. For women age 40 or older, mammography or digital breast tomosynthesis (DBT) should be the initial examination. Ultrasound is usually added as a complementary examination, with some exceptions. For women age 30 to 39, either mammogram or ultrasound may be used as the initial examination on the basis of institutional preference. For women age 30 or younger, ultrasound should be the initial examination, with mammography/DBT added when ultrasound shows suspicious findings or if the patient is predisposed to developing breast cancer. For men age 25 or older, mammography/DBT should be performed initially, with ultrasound added as indicated, given the high incidence of breast cancer in men with pathologic nipple discharge. Although MRI and ductography are not usually appropriate as initial examinations, each may be useful when the initial standard imaging evaluation is negative. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment